[Analysis of the prevalence of anticoagulant therapy in patients with cognitive disorders and cerebral amyloid angiopathy (CAA)]. / Analyse zur Häufigkeit einer gerinnungshemmenden Medikation bei Patientinnen mit kognitiven Störungen und zerebraler Amyloidangiopathie (CAA).

OBJECTIVES: To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. MATERIALS AND METHODS: Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. RESULTS: Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9 years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. A total of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). CONCLUSION: CAA is a frequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with a higher number of cortical and subcortical microbleeds.

[Prognostic and diagnostic value of cerebrospinal fluid analysis in neurodegenerative dementia diseases]. / Prognostischer und differenzialdiagnostischer Stellenwert der Liquordiagnostik bei neurodegenerativen Demenzerkrankungen.

Cerebrospinal fluid (CSF) analysis is an important diagnostic tool in the assessment of dementia. For the differentiation of Alzheimer's disease from other etiologies of dementia syndromes, established biological markers could be helpful to confirm a distinctive neuropathology. Whereas negative CSF findings can rule out the majority of primarily neurodegenerative disorders, overlapping biomarker profiles remain a diagnostic challenge. Therefore, it is important to interpret CSF results within a specific clinical context. Furthermore, atypical CSF data can be challenging and require profound knowledge of preanalytics, biomarker profiles and the broad spectrum of diseases associated with cognitive decline. Beyond the Alzheimer's disease clinical spectrum, current studies aim at investigating CSF biomarkers to better differentiate tauopathies, TDP43(Transactive response DNA binding protein 43 kDa)-proteinopathies and synucleinopathies.

[Criminal behavior in frontotemporal dementia and Alzheimer's disease]. / Delinquentes Verhalten im Rahmen frontotemporaler Demenzen und der Alzheimer-Erkrankung.

Criminal behavior in older people represents a rare phenomenon. Among older criminals there are many first offenders and 75% are men. Dementia poses one possible origin of delinquency in advanced age. It is unclear how often dementia is the actual cause of delinquency in older age. In studies with older criminals the prevalence of dementia was heterogeneous due to methodological study issues. In the course of the disease 50% of patients with frontotemporal dementia and 10% of patients with Alzheimer's disease commit crimes. The neurobiological origin of delinquency in dementia is poorly understood. On the basis of current study results first delinquency in older age can be explained by impairment of social cognition, difficulties in making appropriate emotional contributions and disturbed control of behavior. Affection of frontal and anterior temporal brain structures seem to be of high relevance. As dementia impairs criminal responsibility psychiatrists are confronted with a forensic evaluation of legal culpability of older criminals. Regarding different etiologies of dementia, specific peculiarities need to be considered in a forensic psychiatric assessment. Especially frontotemporal dementia predisposes towards a wide spectrum of criminal behavior whereas patients with Alzheimer's disease predominantly commit crimes due to cognitive impairment. The review summarizes the present knowledge about criminal behavior in the context of dementia.

[Current findings on the coincidence of cerebral amyloid angiopathy and Alzheimer's disease]. / Aktuelle Befunde zur Koinzidenz von zerebraler Amyloidangiopathie und Alzheimer-Erkrankung.

Cerebral amyloid angiopathy (CAA) is closely related to Alzheimer's disease (AD) despite having distinct pathomechanisms. The CAA modulates cognitive impairment within AD by synergistic effects. The pathophysiologic relations are complex and incompletely understood, possibly due to the heterogeneous nature of CAA with its different subtypes. Both diseases are characterized by a pathologic amyloid metabolism but the pathologic processing of amyloid precursor proteins is distinct. The manifestation of vascular and parenchymal amyloid deposits can either overlap or occur independently and isolated. The investigation of the specific contribution of co-occurring CAA within AD to cognitive deficits requires diagnostic methods that sufficiently identify CAA severity and complexity as well as detailed neuropsychological testing to precisely characterize the cognitive deficits and to draw conclusions regarding their etiology.

[Intracerebral hemorrhage under platelet inhibition and oral anticoagulation in patients with cerebral amyloid angiopathy]. / Intrazerebrale Blutungen unter Plättchenaggregationshemmung und oraler Antikoagulation bei Patienten mit zerebraler Amyloidangiopathie.

Oral anticoagulation in patients with cerebral amyloid angiopathy is a therapeutic challenge. The association of cerebral amyloid angiopathy with intracerebral hemorrhage, a high mortality of intracerebral hemorrhage especially under oral anticoagulation and the high risk of recurrent bleeding require a multidisciplinary approach and a thorough risk-benefit analysis. Vitamin K antagonists increase the risk of intracerebral bleeding and the accompanying mortality by 60% and should be avoided if possible or reserved for special clinical situations (e.g. mechanical aortic valve replacement). Treatment with novel oral anticoagulants and antiplatelet drugs also increases the risk of cerebral bleeding and therefore needs a thorough risk-benefit evaluation. An interventional left atrial appendage closure is a promising therapeutic option especially in patients with an absolute arrythmia with atrial fibrillation. Furthermore, other clinical implications in patients with cerebral amyloid angiopathy are the subject of this review of the literature, such as special characteristics after acute ischemic stroke and the necessary secondary prophylaxis, with previous intracerebral hemorrhage and in patients with cognitive deficits.

[Cognitive deficits following brain tumor radiation therapy]. / Kognitive Defizite nach Strahlentherapie von Hirntumoren.

Brain radiation is an important treatment option for malignant and benign brain diseases. The possible acute or chronic impact of radiation therapy on cognitive performance is important for daily functioning and quality of life. A detailed evaluation of cognitive impairment is important in the context of how to control disease progression. The susceptibility of the hippocampus to radiation-induced neuronal damage and its important role in memory highlight that therapeutic strategies require precision medicine.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

[Alzheimer's disease and epilepsy]. / Alzheimer-Demenz und Epilepsie.

Data regarding the incidence and prevalence of epileptic seizures in Alzheimer's disease show great variability and are clinically underestimated due to their atypical symptomatology. Considering their considerable negative effects on cognition and activities of daily living, epileptic seizures need to be correctly treated. Hypotheses with respect to the pathogenetic mechanisms and associations between Alzheimer's disease and epilepsy are mostly derived from animal experiments. The causal connections are so far insufficiently understood. Data on risk factors are inconsistent due to methodological limitations in studies. Clinical data for these indications show good response to therapy with anticonvulsants and good tolerability in the case of new active substances. When treating epileptic seizures in this patient collective using anticonvulsants, potential adverse effects and possible drug interactions need to be closely monitored.

[Assessment of ability to drive in patients with MCI and dementia]. / Beurteilung der Fahrtauglichkeit bei Patienten mit MCI und demenziellen Syndromen.

People with mild cognitive impairment and dementia are a frequent and continuously increasing patient group in practically all fields of medicine. The associated challenges involve nearly all areas of life in addition to the direct medical treatment. Assessment of the ability to drive in patients with cognitive deficits is becoming increasingly more important. What are the options available to physicians in order to make a valid assessment? Which legal aspects must be taken into consideration? Which rights and obligations arise from the framework conditions? These questions nowadays give rise to great uncertainty for many medical personnel; however, the increasing importance of these problems necessitates a clear procedure, which allows difficult decisions to be made with utmost sovereignty and legal certainty and to be able to give patients and relatives a plausible explanation. Because age is a substantial risk factor for the development of cognitive disorders, the question of the ability to drive is affected not only by neuropsychiatric diseases, such as mild cognitive disorders or dementia but also the frequently occurring somatic comorbidities. Estimation of the ability to drive is therefore a complex approach, which should be standardized in order to appreciate all relevant aspects. It would be desirable to have a practice-oriented algorithm, the formulation of which is the aim of this article. Additionally, we would like to make a contribution to road safety and make medical personnel fully aware of this topic.

[Memantine as add-on medication to acetylcholinesterase inhibitor therapy for Alzheimer dementia]. / Memantin als Add-on-Medikation zur Acetylcholinesteraseinhibitor-Therapie bei Alzheimer-Demenz.

Currently available data indicate superior therapeutic effects of combination treatment for Alzheimer dementia with memantine and acetylcholine esterase inhibitors in certain clinical contexts. Out of five randomized, placebo-controlled, double-blind trials two showed superior therapeutic effects in comparison to monotherapy with acetylcholinesterase inhibitors regarding various domains. Recently published meta-analyses and cost-benefit analyses also showed positive results. Recently published German guidelines for dementia treatment also take these new data into account and recommend combination treatment in patients with severe dementia on stable donepezil medication. This article gives an overview of current evidence for combination therapy.

[Non-withdrawal-related delirium : Evidence on prevention and therapy]. / Das nichtentzugsbedingte Delir : Evidenz zu Prävention und Therapie.

Delirium is a severe and common yet under-diagnosed disorder in the clinical routine. Multiple factors may contribute to the development of delirium, which is associated with increased mortality and high healthcare costs. Treatment of delirium is often provided with delay and limited to pharmacological interventions. This article summarizes the key symptoms for delirium as well as risk factors and highlights the pharmacological and non-pharmacological options for treatment and prevention.

[Evidence-based treatment of psychosis associated with Parkinson's disease]. / Evidenz zur Behandlung der Parkinson-assoziierten Psychose.

Psychotic symptoms in Parkinson's disease are frequent phenomena and are often associated with an immense burden for caregivers, increased risk of nursing home placement and mortality. Treatment of psychotic disorders associated with Parkinson's disease often poses a therapeutic dilemma and necessitates a differentiated risk-benefit assessment as both the reduction of antiparkinsonian drugs and use of antipsychotic drugs can result in deterioration of motor functions. This article gives an overview of relevant clinical aspects and highlights the pharmacological evidence-based treatment options.

Thickness in entorhinal and subicular cortex predicts episodic memory decline in mild cognitive impairment.

Identifying subjects with mild cognitive impairment (MCI) most likely to decline in cognition over time is a major focus in Alzheimer's disease (AD) research. Neuroimaging biomarkers that predict decline would have great potential for increasing the efficacy of early intervention. In this study, we used high-resolution MRI, combined with a cortical unfolding technique to increase visibility of the convoluted medial temporal lobe (MTL), to assess whether gray matter thickness in subjects with MCI correlated to decline in cognition over two years. We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of MCI subjects at initial assessment correlated to change in memory encoding over two years (ERC: r = 0.34; P = .003) and Sub (r = 0.26; P = .011) but not delayed recall performance. Our findings suggest that aspects of memory performance may be differentially affected in the early stages of AD. Given the MTL's involvement in early stages of neurodegeneration in AD, clarifying the relationship of these brain regions and the link to resultant cognitive decline is critical in understanding disease progression.